Evidence map›Paper›PMID 31345255›Full record

ArticleActa neuropathologica communications2019

Dramatic response of BRAF V600E-mutant epithelioid glioblastoma to combination therapy with BRAF and MEK inhibitor: establishment and xenograft of a cell line to predict clinical efficacy.

Yu Kanemaru, Manabu Natsumeda, Masayasu Okada, Rie Saito, Daiki Kobayashi, Takeyoshi Eda, Jun Watanabe, Shoji Saito, Yoshihiro Tsukamoto, Makoto Oishi and 8 more

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PubMed Full text at PMC Publisher
In one paragraph

Article in Acta neuropathologica communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed, 1 pooled it
2.7field-weighted citation impact, top 9% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

42 citing papers in PubMed, 1 synthesis or guideline pooled it, 68 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors at 2 institutions in 2 countries.

Yu KanemaruFrom the Departments of Neurosurgery, Niigata University, 1-757 Asahimachidori, Chuo-ku, Niigata, Japan.
Manabu NatsumedaFrom the Departments of Neurosurgery, Niigata University, 1-757 Asahimachidori, Chuo-ku, Niigata, Japan. mnatsumeda@bri.niigata-u.ac.jp.ORCID 0000-0003-3098-8323
Masayasu OkadaFrom the Departments of Neurosurgery, Niigata University, 1-757 Asahimachidori, Chuo-ku, Niigata, Japan.
Rie SaitoPathology, Brain Research Institute, Niigata University, Niigata, Japan.
Daiki KobayashiFrom the Departments of Neurosurgery, Niigata University, 1-757 Asahimachidori, Chuo-ku, Niigata, Japan.
Takeyoshi EdaFrom the Departments of Neurosurgery, Niigata University, 1-757 Asahimachidori, Chuo-ku, Niigata, Japan.
Jun WatanabeFrom the Departments of Neurosurgery, Niigata University, 1-757 Asahimachidori, Chuo-ku, Niigata, Japan.
Shoji SaitoFrom the Departments of Neurosurgery, Niigata University, 1-757 Asahimachidori, Chuo-ku, Niigata, Japan.
Yoshihiro TsukamotoFrom the Departments of Neurosurgery, Niigata University, 1-757 Asahimachidori, Chuo-ku, Niigata, Japan.
Makoto OishiFrom the Departments of Neurosurgery, Niigata University, 1-757 Asahimachidori, Chuo-ku, Niigata, Japan.
Hirotake SaitoDepartment of Radiology and Radiation Oncology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
Masayuki NagahashiDivision of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
Takahiro SasakiDepartment of Neurosurgery, Northwestern University, Chicago, IL, USA.
Rintaro HashizumeDepartment of Neurosurgery, Northwestern University, Chicago, IL, USA.
Hidefumi AoyamaDepartment of Radiology and Radiation Oncology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
Toshifumi WakaiDivision of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
Akiyoshi KakitaPathology, Brain Research Institute, Niigata University, Niigata, Japan.
Yukihiko FujiiFrom the Departments of Neurosurgery, Niigata University, 1-757 Asahimachidori, Chuo-ku, Niigata, Japan.
Niigata University · JPNorthwestern University · US

Funding

Targeting histone demethylase activity for the treatment of pediatric brainstem gliomaR01NS093079 · NINDS · NORTHWESTERN UNIVERSITY AT CHICAGO · PI HASHIZUME, RINTARO · 2015 to 2019
$1.5M
Japan Society for the Promotion of Science 17K16632Japan Society for the Promotion of Science 17K17735Japan Society for the Promotion of Science 17K17739Japan Society for the Promotion of Science 19K09476Japan Society for the Promotion of Science 19K18418NINDS NIH HHS R01 NS093079
6 · The paper itself

Abstract

Epithelioid glioblastoma is a rare aggressive variant of glioblastoma (GBM) characterized by a dismal prognosis of about 6 months and frequent leptomeningeal dissemination. A recent study has revealed that 50% of epithelioid GBMs harbor three genetic alterations - BRAF V600E mutation, TERT promoter mutations, and homozygous deletions of CDKN2A/2B. Emerging evidence support the effectiveness of targeted therapies for brain tumors with BRAF V600E mutation. Here we describe a dramatic radiographical response to combined therapy with BRAF and MEK inhibitors in a patient with epithelioid GBM harboring BRAF V600E mutation, characterized by thick spinal dissemination. From relapsed tumor procured at autopsy, we established a cell line retaining the BRAF V600E mutation, TERT promoter mutation and CDKN2A/2B loss. Intracranial implantation of these cells into mice resulted in tumors closely resembling the original, characterized by epithelioid tumor cells and dissemination, and invasion into the perivascular spaces. We then confirmed the efficacy of treatment with BRAF and MEK inhibitor both in vitro and in vivo. Epithelioid GBM with BRAF V600E mutation can be considered a good treatment indication for precision medicine, and this patient-derived cell line should be useful for prediction of the tumor response and clarification of its biological characteristics.

Indexed as

AnimalsAntineoplastic AgentsBrain NeoplasmsCell Line, TumorDrug Therapy, CombinationForecastingGlioblastomaHumansMaleMAP Kinase Kinase KinasesMiceMice, Inbred BALB CMice, NudeMiddle AgedMutationProtein Kinase InhibitorsAntineoplastic AgentsBRAF protein, humanMAP Kinase Kinase KinasesProtein Kinase InhibitorsProto-Oncogene Proteins B-rafBRAF V600EEpithelioid glioblastomaPrecision medicineTargeted therapy

Identifiers

PMID31345255
PMCPMC6659204
OpenAlexW2963355482

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.